Abstract
Experimental studies have suggested that indoxyl sulfate (IS), a protein-bound uremic toxin, may be involved in the development of renal osteodystrophy. evaluate the association between IS levels and biochemical parameters related to mineral metabolism and bone histomorphometry in a cohort of pre-dialysis chronic kidney disease (CKD) patients. This is a post-hoc analysis of an observational study evaluating the association between coronary calcification and bone biopsy findings in 49 patients (age: 52 ± 10 years; 67% male; estimated glomerular filtration rate: 36 ± 17 ml/min). Serum levels of IS were measured. Patients at CKD stages 2 and 3 presented remarkably low bone formation rate. Patients at CKD stages 4 and 5 presented significantly higher osteoid volume, osteoblast and osteoclast surface, bone fibrosis volume and bone formation rate and a lower mineralization lag time than CKD stage 2 and 3 patients. We observed a positive association between IS levels on one hand and the bone formation rate, osteoid volume, osteoblast surface and bone fibrosis volume on the other. Multivariate regression models confirmed that the associations between IS levels and osteoblast surface and bone fibrosis volume were both independent of demographic and biochemical characteristics of the study population. A similar trend was observed for the bone formation rate. Our findings demonstrated that IS is positively associated with bone formation rate in pre-dialysis CKD patients.
Highlights
Experimental studies have suggested that indoxyl sulfate (IS), a protein-bound uremic toxin, may be involved in the development of renal osteodystrophy
Objective: evaluate the association between IS levels and biochemical parameters related to mineral metabolism and bone histomorphometry in a cohort of pre-dialysis chronic kidney disease (CKD) patients
Disturbances of bone and mineral metabolism are common in chronic kidney disease (CKD) patients and are associated with increased morbidity and reduced quality of life.[1,2]
Summary
Experimental studies have suggested that indoxyl sulfate (IS), a protein-bound uremic toxin, may be involved in the development of renal osteodystrophy. IS’s high binding affinity for albumin means that it cannot be efficiently removed by conventional hemodialysis.[6] The role of IS as a uremic toxin was first revealed by its accelerating effects on CKD progression,[7] possibly via a reduction in proximal tubular cell viability due to increased oxidative stress.[8] Iwazaki et al.[9] subsequently used a rat model of kidney failure associated with low bone turnover to show that IS accumulation was related to lower bone formation rate and the down-regulation of osteoblast-related genes This condition was improved by treatment with the oral adsorbent AST-120 (probably by reducing IS levels). No study assessed by bone histomorphometry has been performed to evaluate this hypothesis
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